Strontium ranelate, a divalent strontium salt of ranelic acid, possesses a capacity to both stimulate bone formation and repress bone resorption. Strontium ranelate has been shown in clinical trials to protect against bone loss and to reduce fracture risk in postmenopausal women by both stimulating bone formation and simultaneously suppressing bone resorption. See Meunier et al. (2004) N Engl J Med 350(5): 459-468; and Reginster et al. (2005) J Clin Endocrinol Metab 90(5): 2816-2822. However, the molecular processes by which this is accomplished are poorly characterized.
NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls the transcription of DNA. NF-κB is widely used by eukaryotic cells as a regulator of genes that control cell proliferation and cell survival. NF-κB is well established to be critical for osteoclast development, function and survival. NF-κB also controls many genes involved in inflammation. NF-κB has been found to be chronically active in many inflammatory diseases, such as inflammatory bowel disease, arthritis, sepsis, gastritis, asthma, among others.